Infectious mononucleosis — known popularly as “mono” or “the kissing disease” — has been recognized for more than a century. An estimated 90 percent of mononucleosis cases are caused by the Epstein-Barr virus (EBV), a member of the herpes virus group. Most of the remaining cases are caused by certain other herpes viruses, particularly cytomegalo virus. This fact sheet focuses on mononucleosis caused by EBV. EBV is a common virus that scientists estimate has infected over 90 percent of people aged 40 or older sometime during their lives. These infections can occur with no symptoms of disease. Like all herpes viruses, EBV remains in the body for life after infection, usually kept under control by a healthy immune system. Almost anyone at any age can get mononucleosis. Seventy to 80 percent of all documented cases, however, involve persons between the ages of 15 and 30. Both men and women are affected, but studies suggest that the disease occurs slightly more often in men than in women. Doctors estimate that each year 50 out of every 100,000 Americans have mononucleosis symptoms. Among college students, the rate is several times higher. Mononucleosis does not occur in any particular “season,” although authorities in colleges and schools, where the disease has been well studied, report that they see most patients in the fall and early spring. Epidemics do not occur, but doctors have reported clustering of cases. Transmission: EBV, the virus that causes most cases of mononucleosis, infects and reproduces in the salivary glands. It also infects white blood cells called B cells. Direct contact with virus-infected saliva, such as through kissing, can transmit the virus and result in mononucleosis. Someone with mononucleosis, however, does not need to be isolated. Household members or college roommates have only a slight risk of being infected unless they come into direct contact with the patient’s saliva. A person is infectious several days before symptoms appear and for some time after acute infection. No one knows how long this period of infectiousness lasts, although the virus can be found routinely in the saliva of most people with mononucleosis for at least six months after the acute infection has subsided. It can be detected in the saliva of about 15 percent of people for years after first infection. Symptoms: Symptoms may take between two and seven weeks to develop after exposure to the virus and can last a few days or as long as several months. In most cases, however, they disappear in one to three weeks. In fact, mononucleosis symptoms may be nonexistent or so mild that most people are not even aware of their illness. In adolescents and young adults, the illness usually develops slowly and early symptoms are vague. Symptoms may include a general complaint of “not feeling well,” headache, fatigue, chilliness, puffy eyelids, and loss of appetite. Later, the familiar triad of symptoms appears: fever, sore throat, and swollen lymph glands, especially at the side and back of the neck, but also under the arm and in the groin. A fever of 101.F to 105.F lasts for a few days and sometimes continues intermittently for one to three weeks. (High fever late in the illness suggests bacterial complications.) The swollen lymph glands, varying in size from that of a bean to a small egg, are tender and firm. Swelling gradually disappears over a few days or weeks. The spleen is enlarged in 50 percent of mononucleosis patients, and the liver is enlarged in 20 percent. Tonsillitis, difficulty in swallowing, and bleeding gums may accompany these symptoms. Rarely, jaundice or a rash that lasts one or two days is present. In young children and older adults (more than 35 years old), mononucleosis may be difficult to diagnose because the typical mononucleosis symptoms are not present. A doctor may suspect mononucleosis in older adults, however, if the patient has had a high fever for at least a week, has an enlarged liver, has abnormal liver function studies, or has neurological symptoms. In children, EBV infection can produce a different picture. A child may have a mild sore throat or tonsillitis or have no symptoms at all, and the illness often goes unrecognized by the parent or teacher. Diagnosis: As mononucleosis symptoms appear, the body reacts to the virus in certain distinctive ways that can be detected through laboratory tests. White blood cells called lymphocytes increase in number (a process known as lymphocytes), and atypical-looking (activated) lymphocytes involved in fighting the virus infection are commonly seen in blood samples. The body produces antibodies, or specific proteins, that protect against EBV. Blood tests that measure lymphocytes and antibodies aid in the diagnosis of mononucleosis. In EBV infection, the body’s immune system also produces more of substances called heterophil antibodies (Paul-Bunnell antibodies). These antibodies indicate that an EBV infection is present in the body, but they are not directed against the virus itself and do not serve a protective function. Because other types of infections and immunologic reactions also induce heterophil antibodies, their presence suggests, but does not indicate specifically, an EBV infection. Symptoms play an important role in the diagnosis of mononucleosis. But because this disease can masquerade as other diseases, symptoms can be misleading. They may resemble, for instance, the sore throat of a “strep” infection, the painful stiff neck of meningitis, the abdominal pains of acute appendicitis, the cough and throat lesions of diphtheria, the rash of rubella or measles, or the swollen lymph glands seen in certain forms of cancer. Rapid and inexpensive blood tests can detect heterophil antibodies in about 80 percent of persons with a current or recent infection. These antibodies can appear in sufficient strength to give a positive diagnosis as early as the fourth day and generally by the 21st day of illness. Heterophil antibodies can persist for months, however, so their appearance does not prove current infection. Furthermore, the level of heterophil antibodies in the blood does not correlate with the severity of symptoms. The slide agglutination mono “spot test,” which is widely used to screen for heterophil antibodies, is inexpensive, requires less than three minutes, and can be performed in a physician’s office. Spot tests are generally accurate, but they can give false positive or false negative results. Sometimes, appearance of heterophil antibodies is delayed, and a repeat test may be necessary to establish a diagnosis. Moreover, young children, older adults, and individuals with EBV infections that do not resemble classic mononucleosis are less likely to develop heterophil antibodies. If a patient with negative spot test results is seriously ill or has unusual symptoms, the doctor should conduct additional tests to rule out other illnesses or infections (such as HIV infection, toxoplasmosis or rubella). An EBV serologic profile is a series of blood tests that, if done and interpreted correctly, will provide a definite diagnosis of mononucleosis that is caused by EBV. Appearance of the antibodies specific for EBV proteins correlates with the stages of infection. The profile is highly accurate, but it is expensive. All physicians have access to laboratories that can perform these tests if they are necessary. The single most meaningful test result to confirm a recent EBV infection is the demonstration of immunoglobulin M (IgM) antibodies to an EBV protein called the viral capsid antigen (VCA). This assay can be done several ways, but unfortunately some of the commercial test kits are overly sensitive and give false positive results. Another way to prove recent EBV infection is to have blood collected at two separate time points, preferably at the first sign of symptoms and again three to four weeks later. The doctor will send both blood samples together to a lab for testing. A more than four-fold increase in immunoglobulin G (IgG) antibodies to several of the EBV-VCA proteins indicates recent infection. Treatment and Recovery: Usually, mononucleosis is an acute, self-limited infection for which there is no specific therapy. For years, standard treatment was bed rest for four to six weeks, with limited activity for three months after all symptoms had disappeared. Today, doctors usually only recommend avoiding strenuous exercise. One real hazard of uncomplicated mononucleosis is the possibility of damaging one’s enlarged spleen. Therefore, the patient should avoid lifting, straining, and competitive sports until recovery is complete. A person should limit other activity according to symptoms and how he or she feels. Treatment of the acute phase of the illness is symptomatic and nonspecific because there is no specific drug treatment for mononucleosis. Rest, plenty of fluids to guard against dehydration, and a well-balanced diet are recommended. Doctors usually recommend acetaminophen or ibuprofen for headache, muscle pains, and chills, and salt gargles for sore throats. (Children and adolescents with a fever should not take aspirin because it can increase the risk of Reye syndrome.) Oral steroid drugs such as prednisone can help lessen some of the symptoms of mononucleosis, but because of their potential toxicity, these drugs are best reserved for treating severe complications. Antibiotics are ineffective against viruses, and they should not be prescribed for mononucleosis itself. Some patients with mononucleosis also develop streptococcal (bacterial) throat infections, which should be treated with penicillin or erythromycin. Ampicillin (a form of penicillin) should not be used. When mononucleosis patients take ampicillin, 70 to 80 percent develop a rash for unknown reasons. Although not a true allergic reaction, the rash may be diagnosed as such, and the patient may be instructed unnecessarily to avoid penicillin in the future. More than 90 percent of mononucleosis infections are benign and uncomplicated, but fatigue and weakness that continue for a month or more are not uncommon. The illness may be more severe and last longer in adults over the age of 30. Airway obstruction, rupture of the spleen, inflammation of the heart or tissues surrounding the heart, and severe bone marrow or central nervous system involvement are rare, life-threatening complications that are treated with steroid drugs. If the spleen should rupture, a doctor will immediately have to remove it surgically and start transfusions and other therapy for shock. Although EBV remains in the body indefinitely following a bout of mononucleosis, the disease rarely recurs. Nearly all individuals who have repeated mono-like illnesses either have a seriously impaired immune system, such as transplant recipients, or are actually experiencing sequential infections with different viruses that can provoke similar symptoms. In addition, several scientific studies now have confirmed that EBV does not cause chronic fatigue syndrome. Further Research: Scientists believe that increased knowledge of normal and abnormal immune responses will lead to an understanding of how EBV can cause a relatively benign illness, like mononucleosis, and also play a role in much more serious, sometimes fatal, diseases. Epstein and Barr, two British scientists after whom EBV is named, first found evidence of the virus in B-lymphocytes of patients with a rare form of cancer of the lymph system. This cancer, known as Burkett s lymphoma, occurs primarily in Africa. Scientists have learned a lot about how EBV affects the body’s cells in mononucleosis. EBV is known to increase the number of B-lymphocytes, which have receptors for the virus on their surfaces. The normal response of the body to this increase in B cells is a corresponding increase in T lymphocytes, another component of the immune system, which change in appearance to become atypical cells. Some of these T cells apparently limit the spread of the virus from cell to cell; others suppress the production of the B cells. This suppression is what seems to eliminate the infection. Normally, the T cell response subsides as the patient recovers from mononucleosis.